1. Biochemistry and Chemical Biology
  2. Microbiology and Infectious Disease
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A selective gut bacterial bile salt hydrolase alters host metabolism

  1. Lina Yao
  2. Sarah Craven Seaton
  3. Sula Ndousse-Fetter
  4. Arijit A Adhikari
  5. Nicholas DiBenedetto
  6. Amir I Mina
  7. Alexander S Banks
  8. Lynn Bry
  9. A Sloan Devlin  Is a corresponding author
  1. Harvard Medical School, United States
  2. Brigham and Women's Hospital, United States
Research Article
  • Cited 44
  • Views 8,596
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Cite this article as: eLife 2018;7:e37182 doi: 10.7554/eLife.37182

Abstract

The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.

Article and author information

Author details

  1. Lina Yao

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  2. Sarah Craven Seaton

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    Sarah Craven Seaton, is currently affiliated with Indigo Agriculture, but the research was conducted when she was a Research Associate at Harvard Medical School. The author has no other competing interests to declare.
  3. Sula Ndousse-Fetter

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  4. Arijit A Adhikari

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    Competing interests
    No competing interests declared.
  5. Nicholas DiBenedetto

    Massachusetts Host Microbiome Center, Department of Pathology, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  6. Amir I Mina

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  7. Alexander S Banks

    Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  8. Lynn Bry

    Massachusetts Host-Microbiome Center, Department of Pathology, Brigham and Women's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  9. A Sloan Devlin

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
    For correspondence
    sloan_devlin@hms.harvard.edu
    Competing interests
    A Sloan Devlin, is a consultant for Kintai Therapeutics.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5598-3751

Funding

The Center for Microbiome Informatics and Therapeutics at MIT (Innovation Award)

  • Arijit A Adhikari
  • A Sloan Devlin

The Harvard Digestive Diseases Center (NIH grant P30DK034854)

  • Lina Yao
  • Sarah Craven Seaton
  • Sula Ndousse-Fetter
  • Arijit A Adhikari
  • Nicholas DiBenedetto
  • Lynn Bry
  • A Sloan Devlin

Karin Grunebaum Cancer Research Foundation (Junior Faculty Award)

  • A Sloan Devlin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments involving mice were performed using IACUC approved protocols (Protocol # 2017N000053) at the Brigham and Women's Hospital Center for Comparative Medicine.

Reviewing Editor

  1. Peter Turnbaugh, University of California, San Francisco, United States

Publication history

  1. Received: April 1, 2018
  2. Accepted: July 6, 2018
  3. Accepted Manuscript published: July 17, 2018 (version 1)
  4. Version of Record published: August 6, 2018 (version 2)

Copyright

© 2018, Yao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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